Total Synthesis of (—)-Stemoamide

摘要

A stereocontrolled total synthesis of (—)-stemoamide (1) is presented. The synthesis starts from commercially available (S)-pyroglutaminol (4). A chemoselective iodoboration of 5 was used to access key intermediate 3. The β,γ-unsaturated azepine derivative 2 was obtained via a Pd(0)-catalyzed sp~2— sp~3 Negishi cross-coupling using a Reformatsky nucleophile followed by a ring-closing metathesis reaction. The required C8-C9 trans-stereochemistry of 1 was accessed through a stereoselective bromolactonization/1,4-reduction sequence.